Mass spectrometric data have been indispensable for our work on the chemistry of bacterial cell wall peptidoglycans isolated form penicillin-resistant clinical isolates. One of the most surprising and exciting findings of this field was the recognition by our laboratory that penicillin-resistant clincal strains of pneumococci produce a chemically-abnormal peptidoglycan. Presumably this unexpected alteration is the result of foreign genetic material taken out by the pneumococcal strains in the natural environment. It is conceivable that the drastic alterations in surface chemistry may also influence the interaction of these resistant strains with their human hosts during pneumococcal infections. Another large area of our studies involving transposon mutants of methicillin-resistant staphylococci also relied heavily on the availability of mass spectrometry for structural characterization of peptidoglycan . A number of the auxiliary mutants in which the expression of methicillin resistance was inactivated were found to be in genes that control the chemical composition of staphylococcal peptidoglycan. Since their inactivation results in massive reduction in methicillin resistance, these auxiliary genes are potential targets for new antibacterial agents.